Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection

BackgroundA clinical case is described of growth retardation, severe developmental delay, facial dysmorphic features with microcephaly, as well as congenital cataract, schizencephaly, periventricular calcifications, and epilepsy. MethodsTORCH infection was suspected, but all tests for toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus were negative for the child and her mother; however, an increased level of antibodies against parvovirus B19 was detected in the proband. ResultsChromosomal analysis and array-CGH showed no aberration. Target capture sequencing for COL4A1 and COL4A2 revealed a de novo COL4A1 mutation (c.2123G>T [p.Gly708Val]). The mutation occurred at a highly conserved Gly residue in the Gly-X-Y repeat of the collagen triple helical domain, suggesting that these mutations may alter the collagen IV 112 heterotrimers. The mutation was predicted to be damaging. ConclusionWe suggest that COL4A1 testing should be considered in patients with schizencephaly as well as with phenotype suggesting TORCH infection without any proven etiological factors. Birth Defects Research (Part A) 106:304-307, 2016. (c) 2016 Wiley Periodicals, Inc.